This Program Project is for the analysis of the effect of chemical mediators on the pulmonary mechanics of the unanesthetized guinea pig and subsequently, as appropriate, of the human. The chemical mediators will be produced and studied in the unanesthetized guinea pig and in the human. The mediators to be considered foremost are the primary products of the acute allergic reaction, namely, histamine, slow reacting substance of anaphylaxis (SRS-A) and eosinophil chemotactic factor of anaphylaxis (ECF-A). Attention will also be given to secondary mediators whose presence is dependent upon the nature of the cellular infiltrate or the activation of human plasma protein systems such as the complement, bradykinin-gathering, and fibrinolytic sequences. The availability of certain chemical mediators for study of the pathobiologic effects on pulmonary mechanics requires only the scaling up of established production and purification procedures, while the others need further definition before offering the purity essential for meaningful in vivo study. The mediators, already available, will be examined comparatively in the guinea pig and human models to define their similarities and differences critical for appraisal of additional mediators. BIBLIOGRAPHIC REFERENCES: Paterson, N.A.M., Wasserman, S.I., Said, J.W. and Austen, K.F.: Release of chemical mediators from partially purified human lung mast cells. J. Immunol. 117:1356, 1976. Yurt, R.W., Leid, Jr., R.W. and Austen, K.F.: Native heparin from rat peritoneal mast cells. J. Biol. Chem. 252:518, 1977.